We report here studies of the long-term effects of combined stress in the prenatal and prepubertal periods of development on measures of tonic inflammatory pain in the formalin test and the severity of depression-like behavior, and also the stress reactivity of the hormonal response in adult rats. In addition, the effects of the serotonin (5-HT) reuptake inhibitor fluoxetine and the 5-HT1A receptor agonist buspirone, given chronically to stressed mothers during pregnancy, on various types of adaptive behavior impaired by prenatal stress were assessed in rats of both sexes. The results showed that in rats of both sexes prenatal stress increased the pain response organized at the spinal and supraspinal levels of the central nervous system and that fluoxetine and buspirone normali zed responses. Stress during the prepuberal period of development eliminated the effects of prenatal stress on the inflammatory pain responses integrated at the supraspinal level in adult rats; in these conditions, fluoxetine and buspirone had no effects, in contrast to their antinociceptive actions on the pain response integrated at the spinal level. Stress at prepubertal age eliminated sex-related differences seen in depression-like behavior in prenatally unstressed and prenatally stressed rats given physiological saline. Control adult females and adult females exposed to prenatal stress in the prepubertal period showed increases in the plasma corticosterone level after forced swimming as compared with the basal hormone level, though there were no significant differences in the level of stress reactivity of the hormonal response after forced swimming. Thus, the conditions for stress actions increasing stress resistance in adult rats were identified. Stress in the critical period o f development formed a phenotype with increased stress resistance to inflammatory pain, which was seen in responses organized at the supraspinal level in adult individuals.
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